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Repetitive Head Impact Exposure and Later-Life White Matter Signal Abnormalities: An Investigation in Former NFL Players, Subjects with Alzheimer's Disease, and Cognitively Normal Controls

重复头部撞击暴露和晚年白质信号异常：对前 NFL 球员、阿尔茨海默氏病受试者和认知正常对照的调查

基本信息

批准号：
10406252
负责人：
Michael Alosco
金额：
$ 15.4万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-04-30
项目状态：
已结题

项目摘要

Repetitive head impacts (RHI) are associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). According to research diagnostic criteria for CTE, known as Traumatic Encephalopathy Syndrome (TES), CTE presents with behavior, mood, and/or cognitive symptoms. There is diversity in the presence of symptoms due to differences in pathology and brain regions affected, and mechanisms of the later-life clinical deficits from RHI are ill-defined. As a result, long-term neurological diseases from RHI (e.g., CTE) cannot be detected at this time. White matter signal abnormalities (WMSA) are non-specific magnetic resonance imaging (MRI) markers of pathologies that may be associated with RHI and affect the clinical presentation of CTE. WMSA predict increased risk for Alzheimer's disease (AD) and pathological correlates of WMSA are common in CTE. Our published data linked T1 WMSA with RHI and executive deficits in former National Football League (NFL) players, independent of vascular status. However, multi-modal neuroimaging studies with control and comparison (e.g., AD) groups are needed to clarify the presence, nature, and effects of WMSA in former NFL players. This K23 will use fluid attenuated inversion recovery (FLAIR) and diffusion MRI to examine WMSA as a long-term consequence of RHI that are distinct from AD and affect later-life clinical function. A team of transdisciplinary scientists from Boston University (BU) will address Dr. Alosco's knowledge gaps in areas key for the study of CTE (exposure science, neuroimaging, neuropathology), leading to an R01 to launch his own research program. The K23 will include 30 male symptomatic former NFL players (45-74 years), 30 same-age and vascular risk-matched male normal controls (NC), and 30 same-age and vascular-risk matched males with AD. NC and AD subjects will be without head trauma history. Former NFL players and NC will be from Dr. Stern's (primary mentor) NINDS U01 examining CTE biomarkers. AD subjects will be from the BU AD and CTE Center (ADCTEC) Registry. The ADCTEC outreach core will ensure inclusion of young AD males (45-55 years). All subjects complete medical, cognitive, behavior/mood, neuroimaging evaluations (T1, FLAIR, diffusion, PET), and lumbar puncture, and blood draw. FreeSurfer and Tracts Constrained by Underlying Anatomy will assess lobar volumes and fiber paths. WMSA will be estimated via a Bayesian probability structure. We will test if former NFL players have a distinct pattern of lobar and fiber path WMSA relative to NC and AD, and if regional WMSA predict cognitive, behavior, and mood function. We will examine whether RHI predicts WMSA and fiber path dysintegrity. In the former NFL players, we will test whether WMSA correspond to lobar volume loss and fiber path dysintegrity and explore if WMSA are related to fluid and PET markers of tau. Millions of Americans are exposed to RHI and this study will have a major public health impact by improving knowledge on the neurological sequelae of RHI, which is imperative to facilitate research on the diagnosis, treatment, and prevention of brain diseases, like CTE.

反复头部撞击（RHI）与神经退行性疾病慢性创伤性脑病（CTE）有关。根据CTE的研究诊断标准，称为创伤性脑病综合征（TES），CTE表现为行为，情绪和/或认知症状。由于病理学和受影响的脑区域的差异，存在症状的多样性，并且RHI的晚年临床缺陷的机制不明确。因此，来自RHI的长期神经系统疾病（例如，CTE）此时无法检测到。白色信号异常（WMSA）是可能与RHI相关并影响CTE临床表现的非特异性磁共振成像（MRI）病理标志物。WMSA预测阿尔茨海默病（AD）的风险增加，WMSA的病理相关性在CTE中很常见。我们发表的数据将T1 WMSA与前国家橄榄球联盟（NFL）球员的RHI和执行缺陷联系起来，与血管状态无关。然而，多模态神经成像研究与对照和比较（例如，AD）团体需要澄清WMSA在前NFL球员中的存在、性质和影响。该K23将使用液体衰减反转恢复（FLAIR）和扩散MRI检查WMSA作为RHI的长期后果，与AD不同，并影响晚年临床功能。来自波士顿大学（BU）的一个跨学科科学家团队将解决Alosco博士在CTE研究（暴露科学，神经影像学，神经病理学）关键领域的知识差距，导致R 01启动自己的研究计划。K23将包括30名男性症状性前NFL球员（45-74岁），30名相同年龄和血管风险匹配的男性正常对照（NC），以及30名相同年龄和血管风险匹配的AD男性。NC和AD受试者将无头部创伤史。前NFL球员和NC将从斯特恩博士（主要导师）NINDS U 01检查CTE生物标志物。AD受试者将来自BU AD和CTE中心（ADCTEC）登记研究。ADCTEC外展核心将确保纳入年轻的AD男性（45-55岁）。所有受试者均完成医学、认知、行为/情绪、神经影像学评价（T1、FLAIR、弥散、PET）、腰椎穿刺和抽血。FreeSurfer和受基础解剖结构约束的血管束将评估肺叶体积和纤维路径。WMSA将通过贝叶斯概率结构进行估计。我们将测试前NFL球员是否具有相对于NC和AD的脑叶和纤维路径WMSA的独特模式，以及区域WMSA是否预测认知，行为和情绪功能。我们将研究RHI是否预测WMSA和光纤路径不完整性。在前NFL球员中，我们将测试WMSA是否对应于肺叶体积损失和纤维路径不完整性，并探索WMSA是否与tau的流体和PET标记物相关。数以百万计的美国人暴露于RHI，这项研究将通过提高对RHI神经系统后遗症的认识来产生重大的公共卫生影响，这对于促进对CTE等脑部疾病的诊断，治疗和预防的研究至关重要。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Long-Term Changes in Brain Connectivity Reflected in Quantitative Electrophysiology of Symptomatic Former National Football League Players.

有症状的前国家橄榄球联盟球员的定量电生理学反映了大脑连接的长期变化。

DOI：
10.1089/neu.2022.0029
发表时间：
2023
期刊：
Journal of neurotrauma
影响因子：
4.2
作者：
Liang,Bo;Alosco,MichaelL;Armañanzas,Ruben;Martin,BrettM;Tripodis,Yorghos;Stern,RobertA;Prichep,LeslieS
通讯作者：
Prichep,LeslieS

Incidence of and Mortality From Amyotrophic Lateral Sclerosis in National Football League Athletes.

DOI：
10.1001/jamanetworkopen.2021.38801
发表时间：
2021-12-01
期刊：
JAMA network open
影响因子：
13.8
作者：
Daneshvar DH;Mez J;Alosco ML;Baucom ZH;Mahar I;Baugh CM;Valle JP;Weuve J;Paganoni S;Cantu RC;Zafonte RD;Stern RA;Stein TD;Tripodis Y;Nowinski CJ;McKee AC
通讯作者：
McKee AC

Association Between Leptin, Cognition, and Structural Brain Measures Among "Early" Middle-Aged Adults: Results from the Framingham Heart Study Third Generation Cohort.